Individual differences in drug abuse vulnerabilities among humans are likely to display genetic as well as environmental components. During this year, these investigators continued to explore possible roles of allelic variants at candidate gene loci in possibly contributing to human individual differences in drug abuse vulnerability, made substantial progress with genome scanning approaches to identifying previously-unanticipated gene loci conferring drug abuse vulnerabilities, developed and validated microarray-based strategies for assessing single nucleotide polymorphisms in pooled samples, worked to overcome the limitations of the sibship collections possible in the intramural setting, and continued to made major advances in providing simulations and modeling for the power of genomme-wide and focused association/linkage-disequilibrium based genome scanning. Work during this year identified candidate regions on several human chromosomes using high-density SNP and SSLP-based linkage-disequilibrium based genome scanning. Data is consistent with the emerging models that genetic influences are polygenic with few major gene influences. Chromosome 1 and 11 regions previously nomninated in alcoholism studies may also play roles in polysubstance abuse vulnerability. This work represents one of the first high-density genome scans for genomic regions containing polysubstance abuse vulnerability alleles, and a novel approach to genome scanning for complex disorcer genetics.